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Vite Laboratory

The focus of the Vite lab is to improve the characterization and treatment of neurological Niemann-Pick Disease, Penn Vet, Vite Laboratorydiseases by studying naturally-occurring feline and canine models of human diseases.

Our lab develops and identifies ante-mortem biochemical and nuclear magnetic resonance markers of disease severity and progression and uses these markers to evaluate the efficacy of gene therapy, cell-based therapy, and pharmacotherapy to treat disease. 

Cholesterol and the cat brain


Niemann-Pick type C (NPC) disease is a progressive neurological disorder Vite Laboratory, Niemann Pick Diseasecharacterized by dementia and ataxia, hepatic and pulmonary disease, and death typically within the first or second decade. Over 300 disease-causing mutations have been identified in the lysosomallylocalized proteins NPC1 and NPC2, which result in:
  • Altered regulation of cholesterol homeostasis
  • Lysosomal storage of cholesterol, gangliosides, and sphingosine
  • Neurodegeneration
Despite the identification of causative mutations, the pathogenesis is not clear and therapies to successfully treat NPC disease have been ineffective to date.
The critical barriers to developing effective treatment for Niemann-Pick type C (NPC) disease are:
  • The lack of natural history studies due to the relatively low incidence and the heterogeneity of disease in human patients
  • An insufficient understanding of how the defect in cholesterol transport results in the phenotype
  • The paucity of validated surrogate markers of brain disease that can be monitored as secondary clinical endpoints
  • The dearth of candidate compounds which substantially improve neurological disease in animal models

Dr. Vite’s laboratory addresses these barriers first by utilizing a unique large animal model of NPC disease for which a breeding colony and natural history data exist.

Second, the well-characterized feline model allows for the identification and validation of biochemical and nuclear magnetic resonance surrogate makers of neurological disease due to its large size and its accurate recapitulation of human disease. These biochemical markers provide insight into CNS disease pathogenesis. Third, recent studies in both the feline and murine models have revealed substantial therapeutic benefit of 2-hydroxypropyl-ß-cyclodextrin (HPßCD) on NPC disease.

HPßCD therapy in NPC disease

Dr.Vite is funded by an R01 (NIH) to rigorously evaluate the mechanistic, pharmacologic, and toxicity issues associated with HPßCD therapy in NPC disease.

His laboratory discovered that intrathecal administration of HPßCD ameliorates all clinical aspects of neurological disease at least up to a year of age (untreated cats need to be euthanized at 24 weeks of age for the neurological disease) and that neuronal storage of cholesterol was substantially reduced. They also identified a dose-related toxic effect of HPßCD on hearing threshold.

The remarkable therapeutic effect of HPßCD in affected cats has led to its use as an FDA-designated orphan drug and to plan for a controlled clinical trial in NPC patients. The availability of effective intrathecal therapy also allows for the identification and validation of biochemical markers of disease severity and therapeutic effect and to further understand the mechanism of action of cholesterol storage in CNS disease.

Effect of cyclodextrin therapy on serum oxysterol concentrations in treated cats

In collaboration with Washington University in St Louis, Dr. Vite has evaluated the effect of cyclodextrin therapy on serum oxysterol concentrations in treated cats, to help validate oxysterol concentrations as the first blood test available for diagnosing NPC in newborns.

His laboratory has also identified altered betaamyloid processing in the spinal fluid of treated cats compared to untreated cats in collaboration with the University of Gothenburg. Their ongoing work is focused on identifying the mechanism of action of cyclodextrin in CNS therapy as well as on hair cell function of the inner ear.

Predicting seizures in dogs

Idiopathic canine epilepsy is the most common neurological disorder seen in the neurology clinic and the prevalence, age of onset, and signs of the naturally occurring canine disease are similar to those observed in humans.

The majority of dogs with recurrent seizures have no intracranial structural defect, no demonstrable serum or spinal fluid abnormalities, and no interictal neurological deficits, consequently, the disease is “idiopathic”.

Affected dogs usually have their first seizure during the first three years of life (approximating adolescence to early adulthood), and exhibit recurring motor, autonomic, and/or behavioral signs throughout life.

Electroencephalographic studies reveal focal spikes and spike/wave discharges in canine epilepsy, but are technically difficult to document due to the need for behavioral training or sedation to minimize recording artifacts.

Despite spending as little as 0.01% of their lives having seizures, dogs and people with epilepsy take antiepileptic drugs (AEDs) on a daily basis for years to decades. Many experience significant AEDrelated side effects, and approximately 1/3 of patients continue to have seizures despite treatment. To reduce exposure to AED, epilepsy could be more effectively treated by responsively delivering AEDs only during periods of increased seizure likelihood.

Dr. Vite is funded by a grant from NeuroVista Corporation to implant cortical electrodes and to use mathematical electroencephalo-grambased algorithms to detect (and develop ways to predict) the onset of seizures in dogs.

Preliminary data from these studies have resulted in a well-scored U01 grant (14 percentile) that includes co-investigators at the Mayo Clinic, University of Minnesota, and University of Pennsylvania and for which Dr. Vite, at the Veterinary School and Dr. Litt, at the School of Medicine, are coinvestigators.

Their expectation is that this novel investigation will enable the development of a seizure prediction device for human and animal patients which will limit the requirement for AEDs to those times when a seizure is expected.

It is also anticipated that the ability to record continuous intracranial activity in dogs via telemetry will aide in developing evidence-based methods to treat better both status epilepticus and epilepsy.

Stein, V. M., Crooks, A., Ding, W., Prociuk, M., O'Donnell, P., Bryan, C., Sikora, T., Dingemanse, J., Vanier, M. T., Walkley, S. U., Vite, C. H. Miglustat improves purkinje cell survival and alters microglial phenotype in feline Niemann-Pick disease type C J Neuropathol Exp Neurol 71: 434-48, 2012.

Brinkmalm, G., Portelius, E., Ohrfelt, A., Mattsson, N., Persson, R., Gustavsson, M. K., Vite, C. H., Gobom, J., Mansson, J. E., Nilsson, J., Halim, A., Larson, G., Ruetschi, U., Zetterberg, H., Blennow, K., Brinkmalm, A. An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid beta and amyloid precursor protein in human and cat cerebrospinal fluid J Mass Spectrom 47: 591-603, 2012.

Mattsson, N., Olsson, M., Gustavsson, M. K., Kosicek, M., Malnar, M., Mansson, J. E., Blomqvist, M., Gobom, J., Andreasson, U., Brinkmalm, G., Vite, C., Hecimovic, S., Hastings, C., Blennow, K., Zetterberg, H., Portelius, E. Amyloid-beta metabolism in Niemann-Pick C disease models and patients Metab Brain Dis : , 2012.

Vite, C. H., Wang, P., Patel, R. T., Walton, R. M., Walkley, S. U., Sellers, R. S., Ellinwood, N. M., Cheng, A. S., White, J. T., O'Neill, C. A., Haskins, M. Biodistribution and pharmacodynamics of recombinant human alpha-L-iduronidase (rhIDU) in mucopolysaccharidosis type I-affected cats following multiple intrathecal administrations Mol Genet Metab 103: 268-74, 2011.

Davis, K. A., Sturges, B. K., Vite, C. H., Ruedebusch, V., Worrell, G., Gardner, A. B., Leyde, K., Sheffield, W. D., Litt, B. A novel implanted device to wirelessly record and analyze continuous intracranial canine EEG Epilepsy Res 96: 116-22, 2011.

Lewis, M. J., Williams, D. C., Vite, C. H. Evaluation of the electroencephalogram in young cats Am J Vet Res 72: 391-7, 2011.

Vite, C. H., Cross, J. R. Correlating magnetic resonance findings with neuropathology and clinical signs in dogs and cats Vet Radiol Ultrasound 52: S23-31, 2011.

Ward, S., O'Donnell, P., Fernandez, S., Vite, C. H. 2-hydroxypropyl-beta-cyclodextrin raises hearing threshold in normal cats and in cats with Niemann-Pick type C disease Pediatr Res 68: 52-56, 2010.

Magnitsky, S., Vite, C. H., Delikatny, E. J., Pickup, S., Wehrli, S., Wolfe, J. H., Poptani, H. Magnetic resonance spectroscopy of the occipital cortex and the cerebellar vermis distinguishes individual cats affected with alpha-mannosidosis from normal cats NMR Biomed 23: 74-9, 2010.

Porter, F. D., Scherrer, D. E., Lanier, M. H., Langmade, S. J., Molugu, V., Gale, S. E., Olzeski, D., Sidhu, R., Dietzen, D. J., Fu, R., Wassif, C. A., Yanjanin, N. M., Marso, S. P., House, J., Vite, C., Schaffer, J. E., Ory, D. S. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease Sci Transl Med 2: 56ra81, 2010.